It is known that radiolabeled antibodies specific to antigens which are either produced or associated with tumors can be used to localize tumors. U.S. Pat. No. 3,927,193 to Hansen et al discloses a method of tumor localization using labeled antibodies to carcinoembronic antigen (CEA), but provides examples of its use only in animals. Goldenberg et al, New Eng. J. Med., 298, 1384 (1978), reported success in clinical trials of tumor detection and localization by scintillation scanning of patients receiving radiolabeled antibodies to CEA. A special scanner subtraction technique with other radionuclides to compensate for interstitial and blood-pool background activity was considered essential for unequivocal tumor localization using that method.
However, even this most recent and successful tumor localization and detection process has certain disadvantages which limit its use. The labeled antibodies are very large molecules which also carry cross-reactive antigenic determinants, and it is quite difficult to reduce cross-reactivity below 15% and to achieve specificity for a particular antigen of higher than 70%. The subtraction technique used by Goldenberg et al involves the use of a different radionuclide attached to a carrier having kinetics of transport and distribution different from the labeled specific antibody. In addition, the background-compensating material must be injected prior to each photoscan, which exposes the patient to increased levels of radioactivity and discomfort. A further limitation of the prior art methods is that antibody molecules cannot pass the blood-brain barrier, which means that intravenously injected antibodies cannot be used to localize intracranial tumors. Radioactively labeled fragments obtained by cleavage of antibodies specific to cardiac myosin have been used to determine the location and size of myocardial infarcts, in U.S. Pat. No. 4,036,945 to Haber.
Tumor radiotherapy using labeled antibodies has been suggested by many, and an indication of its success in a single multimodal therapeutic clinical use is reported by Ettinger et al., Cancer Treat. Rep., 63, 131 (1979). The use of the boron-labeled antibodies in therapy is reported by Hawthorne et al., J. Med. Chem., 15, 449 (1972), but the combined incorporation of boron and a radioisotope for localization is not suggested.
A need continues to exist for a rapid, high resolution method of tumor detection and localization, one which ideally is capable of detecting and locating more than one type of tumor or tumor cells using a single injection, and which avoids other disadvantages of the prior art methods.